The apparent diffusion coefficient changes with time after hypoxic-ischemic brain injury. In this study, we quantitatively examined the relationship between the apparent diffusion coefficient and postnatal age for neonates with hypoxic-ischemic encephalopathy and poor outcome, and determined the postnatal age at which these values cannot be distinguished from those of neonates without hypoxic-ischemic encephalopathy (pseudonormalization time). Diffusion-weighted brain images were obtained from clinical scans of term neonates with hypoxic-ischemic encephalopathy and poor outcome (12 neonates, 23 scans) and from control subjects (30 neonates, 31 scans). The correlation between apparent diffusion coefficient and postnatal age was investigated for several brain regions. Pseudonormalization times were determined (1) from the intersection of the regression lines for the hypoxic-ischemic encephalopathy and control groups, as well as (2) from intrasubject apparent diffusion coefficient changes between two scans within a small subgroup. Pseudonormalization times from the regression ranged from 8.3 +/- 1.9 days to 10.1 +/- 2.1 days. Slightly (approximately 1 day) longer values were obtained from the intrasubject analysis. The results suggest that, although abnormally decreased apparent diffusion coefficient values may be evident from approximately 2 days to almost 1 week of postnatal age, abnormally elevated values may not be apparent until late in the second week of life.